Case 712 -- A 46 year old female with shortness of breath

Contributed by Isil Z Yildiz, MD and Lydia C. Contis, MD

CLINICAL HISTORY

Patient is a 46-year-old female with no significant past medical history. She presented to an outside hospital with a three day history of shortness of breath and palpitations. A chest x-ray revealed bilateral lung infiltrates. She was subsequently intubated for respiratory failure and sedated. She also had black, tarry stools and bloody orogastric tube output, and was subsequently admitted to an outside hospital intensive care unit for sepsis. Reported initial complete blood count values included a hemoglobin value of 7.4 gm/dl, platelet count of 13x10E+9/L, and white blood cell count of 10.3x10E+9/L, The peripheral blood differential reportedly demonstrated 15% blasts. She was transferred to the intensive care unit at UPMC for further management. A bone marrow biopsy was performed for further evaluation.

Peripheral Blood:

The results of the complete blood count (CBC) are illustrated in Table 1. These demonstrate an elevated white blood cell count with 58% blasts along with a macrocytic anemia and thrombocytopenia.

The bone marrow differential demonstrated numerous blasts (50% by manual differential of 300 cells) along with complete maturation of myeloid cells (Table 2). The blasts demonstrated morphologic features similar to those seen in peripheral blood (Figure 3). The bone marrow biopsy was normocellular for age (50-60% cellular) (Figure 4 and Figure 5).

FISH analysis was positive for the RUNX1T1/RUNX1 gene rearrangement in 196 of the 201 interphase cells examined (97.5%) (Figure 8). FISH analysis was negative for the PML/RARA gene rearrangement in all of the interphase cells examined in the specimen.

Classical cytogenetics demonstrated the presence of a t(8;21)(q22;q22), inv(9)(p11q13) . The analysis revealed an abnormal female bone marrow chromosome with a pericentric inversion of one chromosome 9 (Figure 9, red arrow) along with a translocation between the long arms of chromosomes 8 and 21 (Figure 9,black arrows). The inv(9)(p11q13) chromosome occurs in about 2% of the population and is considered to be a normal variant.